Changes in matrix metalloproteinases and their inhibitors during interferon-beta treatment in multiple sclerosis.
Matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs) play a key role in the pathogenesis of multiple sclerosis (MS) and have been proposed as biomarkers of response to therapy. We investigated serum levels of several MMPs and TIMPs in 43 relapsing-remitting MS (RRMS) patients undergoing interferon-beta (IFN-b) treatment and classified as responders and non-responders based on clinical criteria. Levels of MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 were determined by ELISA before treatment and after 3, 6, 12, and 24 months of therapy. Neutralizing antibodies were determined by the myxovirus A induction bioassay. Treatment with IFN-b induced changes in levels of MMP-9 and TIMP-1. In contrast to non-responders, IFN-b resulted in an early and sustained increase in TIMP-1 levels in MS patients who showed clinical response to IFN-b. The early and sustained increase in TIMP-1 levels could be a marker of the response to IFN-b during the first 2 years of treatment.
Comabella
Manuel
M
Unitat de Neuroimmunologia Clínica, CEM-Cat, Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain. mcomabel@ir.vhebron.net
Río
Jordi
J
Espejo
Carmen
C
Ruiz de Villa
Mamen
M
Al-Zayat
Hammad
H
Nos
Carlos
C
Deisenhammer
Florian
F
Baranzini
Sergio E
SE
Nonell
Lara
L
López
Cristina
C
Julià
Eva
E
Oksenberg
Jorge R
JR
Montalban
Xavier
X
D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020783:Matrix Metalloproteinase 7 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy*; D011446:Prospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood
D007155:Immunologic Factors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D016899:Interferon-beta; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9